This research involves the study of enzymes released by bacteria which catalyze the cleavage of human immunoglobulin A (IgA) antibody. Because of the central role played by IgA in the immune defense of mucosal surfaces, these enzymes have the potential of interfering with IgA function. It is proposed that the IgA protease may represent a means by which microorganisms defend themselves against immune responses mediated by IgA. IgA proteases are neutral proteolytic enzymes which enter the external environment of the bacteria. While Streptococcus sanguis is the organisms of principal interest in this proposal, IgA proteases also are produced by the pathogenic neisserial species N. gonorrhoeae and N. meningitidis. All IgA proteases yet examined have specificity for only human IgA, and only the IgA subclass of this isotype. The enzymes cleave prolyl-threonyl peptide bands critically situated in the hinge region of IgA, between the Fc and Fab regions of the molecule. Specifically, we are concentrating our research efforts in determining how IgA proteases alter antibody function in the human IgA isotype, developing an assay system for these enzymes of highly restricted substrate specificity, and determining the role which extra chromosomal DNA may have in enzyme production.